Hypoxic/hypercapnic drive studies will be continued to further elucidate responses associated with drug studies, i.e., Pentobarbital, Provera, alcohol, etc. Additionally we plan to study hypoxic- hypercapnic response in normal-responder and low-responder normal subjects with exercise stimulus, and the effect of external flow resistance on hypoxic drive in this same group of low-and normal- response subjects. This latter study relates to the postulated reactions to airway obstruction in the "pink-puffer" and "blue-bloater" patient classification. A mathematical analysis of oxygen transfer to blood flowing in man- made silicone rubber capillaries 7 to 12.5 microns diameter shows oxygen transfer characteristics similar to lung capillaries and also that it is theoretically possible to measure O2 reaction rate with blood, O,in the silicone capillaries; current efforts are to measure O using whole blood. Use of impediment and residence time distribution studies will be expanded to determine the effect of ventilatory patterns on steady-state DCO measurements. Testing will be done at two breathing frequencies at constant tidal volume; additionally the effect of inspired gas distribution on DCO will be determined by tracer gas-mass spectrometric techniques to determine inspired gas residence time distribution, minute ventilation, and measured DCO relationships. The objective is to use DCO and distribution of inspired gas for detecting early alveolar dysfunction.